Observational Follow up of Prior HPV Vaccinees

NCT ID: NCT02811068

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 93 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2017-12-31

Brief Summary

HPV vaccines have been included in the national immunisation schedule since 2008, firstly as the Cervarix vaccine which protects against two HPV types and in 2012 as the Gardasil vaccine which offers protection against a further two HPV types. This study will assess whether booster doses are indicated to protect females throughout their lifetime or if the vaccinations offered in early adolescence provide this by following up a cohort from a previous study where female adolescents were vaccinated 5-7 years ago.

Detailed Description

Since September 2008, Human Papillomavirus (HPV) vaccines have been offered as part of the UK national immunisation schedule to adolescent females, first as three doses of a bivalent vaccine (Cervarix) covering the two most common strains (HPV16 and 18). Subsequently a quadrivalent vaccine was given in 2012 (Gardasil) incorporating a further two HPV types (HPV6 and 11). Between 2009 and 2011, the National Vaccine Evaluation Consortium (NVEC) conducted a randomised, observer-blinded parallel group study to evaluate the immunogenicity of the two HPV vaccines in terms of humoral immune responses against vaccine and non-vaccine incorporated HPV genotypes. The investigators plan to approach the participants of the original study as part of a follow up study to assess the duration of the humoral immune response elicited to the HPV vaccines; specifically, comparing the breadth and magnitude of antibody responses against vaccine and non-vaccine incorporated genotypes 5.7-6.8years on from their first dose of vaccine.

Long-term follow up studies have been conducted up to 9.4 years post vaccination for example in a multicentre double-blinded trial evaluating the long term efficacy of the Cervarix vaccine, which demonstrated 95-100% sustained efficacy against incident infection and CIN1+/2+ lesions whilst antibody titres were above those seen with natural infection adding confidence to the long term efficacy of this vaccine . The quadrivalent vaccine has been evaluated in long term follow up studies for example in a continuation of the Future II study at 9 years post first dose, whereby ≥94% of samples were seropositive for types 6,11 and 16 and 60% for HPV18 according to a cut-off negative serostatus value decided on by a selection of naïve and seropositive sera. There was also minimal difference in titres compared to months 18 and 48, representing a stable plateau of seroprotective titres. There are only two studies that have examined the duration of antibody responses against non-vaccine genotypes beyond 12 months: one comparing antibody titers elicited by both HPV vaccines against HPV31 and HPV45 in 18-26 year old women 24 months post first dose and one describing HPV31 seropositivity in 18-25 year old women at 48 months. This study will therefore provide unique data for the age group that HPV vaccination is offered to in the UK, in terms of vaccine incorporated genotypes as there are a limited number of follow up studies evaluating the 12-15 year old age group, as well as assessing the duration of antibody responses against non-vaccine types which has been far less extensively studied in all age groups.

A minimum antibody titre that correlates with HPV vaccine efficacy has not been defined; that is, a so-called correlate of protection. For HPV16 and HPV18 this is, in part, due to the high levels of HPV antibody generated following vaccination and the lack of breakthrough infections in vaccine trials. For non-vaccine genotypes where efficacy is only partial, further information on the breadth, magnitude and duration of such antibody specificities is required before a correlate (or surrogate) of protection can be established .

There is evidence to suggest robust immunological memory from studies looking at booster doses of HPV vaccine, which could be introduced into the UK programme to ensure protection throughout a women's sexual lifetime. For instance, in a follow up study assessing the immunological response to a booster dose of Cervarix seven years following immunisation with a three dose schedule, a strong memory B cell response persists after vaccination, giving rise to significantly higher GMTs than observed following the first dose of the bivalent vaccine. A significant fold-increase in GMTs was also observed with a booster dose following two doses of the quadrivalent vaccine, though GMTs were higher following a bivalent booster.

This follow up study will begin to address the question of long term durability of HPV vaccine antibody responses afforded by the HPV vaccines in the target age group in the UK population and therefore whether changes need to be made to the current national schedule.

Conditions

Human Papillomavirus Virus

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Venepuncture

Collection of single blood sample to assess antibody persistence over time

venepuncture

Intervention Type: OTHER

single venepuncture

Interventions

venepuncture

single venepuncture

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Participant is willing and able to give written informed consent for participation.
• Females originally enrolled in the randomised parallel group study

Exclusion Criteria

• Known bleeding diathesis (or any condition that may be associated with a prolonged bleeding time).
• Any other significant condition or circumstance which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Public Health England

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Coates

Role:

Public Health England

Locations

Gloucestershire primary care

Gloucestershire, Gloucestershire, United Kingdom

Hertfordshire primary care

Hertfordshire, Hertfordshire, United Kingdom

Countries

United Kingdom

Other Identifiers

HPVfollowup

Identifier Type: -

Identifier Source: org_study_id